J Cancer 2018; 9(15):2612-2624. doi:10.7150/jca.24959

Research Paper

Roles of B7-H3 in Cervical Cancer and Its Prognostic Value

Sai Han1, Xuejiao Shi2, Lu Liu1, Liju Zong1, Jingjing Zhang1, Qian Chen1, Qiuhong Qian1, Li Chen1, Ying Wang1, Jing Jin1, Yana Ma1, Baoxia Cui1, Xingsheng Yang1, Youzhong Zhang1✉

1. Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
2. Department of Rheumatism and Immunology, General Hospital of Tianjin Medical University, Tianjin 300000, P.R. China.

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Han S, Shi X, Liu L, Zong L, Zhang J, Chen Q, Qian Q, Chen L, Wang Y, Jin J, Ma Y, Cui B, Yang X, Zhang Y. Roles of B7-H3 in Cervical Cancer and Its Prognostic Value. J Cancer 2018; 9(15):2612-2624. doi:10.7150/jca.24959. Available from http://www.jcancer.org/v09p2612.htm

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B7-H3, which has been reported to be a co-regulatory ligand of the B7 family, can suppress T cell-mediated immunity and has also been reported to be expressed in many malignancies. In this study, we found that B7-H3 was primarily expressed in the cytoplasm of cervical cancer cells and was associated with deep stromal invasion (P=0.0013). The disease-free survival data showed that cervical cancer patients whose tumours were positive for B7-H3 expression had higher mortality rates compared with patients whose tumours lacked B7-H3 expression (P=0.0317), representing an advantage over P16 (P=0.3486). In contrast, the level of serum B7-H3 was low in cases of cervical intraepithelial neoplasia and cervical cancer. The silencing of B7-H3 in the SiHa, CaSki and H8 cell lines inhibited cell proliferation and enhanced apoptosis, while the over-expression of B7-H3 in HeLa cells showed inverse changes. These changes were partially due to the regulation of cell cycle- and apoptosis-related proteins, such as E2F, P21, P16, PARP-1, Caspase-8, Bax, Bcl-2 and Bcl-xl. The results of in vivo experiments revealed that the knockdown of B7-H3 in tumour cells suppressed SiHa cell growth in nude mice. Overall, B7-H3 is involved in the development and progression of cervical intraepithelial neoplasia and cervical cancer through its effects on the cell cycle and apoptosis, which are mediated via the E7/Rb pathway. B7-H3 also has the potential to be a useful prognostic marker for patients with cervical cancer.

Keywords: B7-H3, cervical cancer, E7/Rb pathway, proliferation, apoptosis.